Glycinergic feedback enhances synaptic gain in the distal retina

Abstract

Key pointsr This study provides experimental evidence that glycinergic interplexiform cells create a centrifugal feedback loop in the vertebrate retina that regulates the transmission of glutamatergic signals between photoreceptors and second-order neurons.r This mechanism serves to reduce glutamate uptake and enhance glutamate release. r Glycine receptors containing the GlyRα3 subunit are expressed on bipolar cell dendrites, and their activation leads to a depolarizing response in a group of rod-dominated ON bipolar cells, and hyperpolarizing responses in OFF bipolar cells.r Using strychnine to block endogenous glycine feedback reduces the amplitudes of light-evoked responses in both ON and OFF bipolar cells, indicating that glycine feedback regulates signal propagation in the distal retina.r Glycinergic feedback provides a neural mechanism that enhances synaptic gain and improves visual sensitivity.Abstract Glycine input originates with interplexiform cells, a group of neurons situated within the inner retina that transmit signals centrifugally to the distal retina. The effect on visual function of this novel mechanism is largely unknown. Using gramicidin-perforated patch whole cell recordings, intracellular recordings and specific antibody labelling techniques, we examined the effects of the synaptic connections between glycinergic interplexiform cells, photoreceptors and bipolar cells. To confirm that interplexiform cells make centrifugal feedback on bipolar cell dendrites, we recorded the postsynaptic glycine currents from axon-detached bipolar cells while stimulating presynaptic interplexiform cells. The results show that glycinergic interplexiform cells activate bipolar cell dendrites that express the α3 subunit of the glycine receptor, as well as a subclass of unidentified receptors on photoreceptors. By virtue of their synaptic contacts, glycine centrifugal feedback increases glutamate release from photoreceptors and suppresses the uptake of glutamate by the type 2A excitatory amino acid transporter on photoreceptors. The net effect is a significant increase in synaptic gain between photoreceptors and their second-order neurons. Abbreviations DHKA, dihydrokainic acid; EAAT2A, type 2A excitatory amino acid transporter; EPSC, excitatory postsynaptic current; GlyRα3, glycine receptor α3 subunit; IPL, inner plexiform layer; LED, light emitting diode; OCT compound, optimal cutting temperature compound; OPL, outer plexiform layer; TEA, tetraethylammonium.

Nonlinearities in retinal bipolar cells shape the encoding of artificial and natural stimuli

“…For similar reasons, also horizontal cells and the rarely observed interplexiform cells, which are located in the inner retina and provide glycinergic input onto the dendrites of bipolar cells (Maple and Wu, 1998), are unlikely to generate the nonlinearity. Activating glycine receptors through interplexiform cells hyperpolarizes OFF bipolar cells (Jiang et al, 2014), whereas the nonlinear responses to patterned-spot stimulation consisted of depolarization events. And horizontal cells have large receptive fields (500 to 1600 µm) in the salamander retina (Lasansky and Vallerga, 1975;Zhang et al, 2006), and thus, they are expected to be more activated under global compared to a local stimulation ( Figure 8E-H).…”

What the Salamander Eye Has Been Telling the Vision Scientist’s Brain

“…There also have been observations of glycine receptors at the dendrites of bipolar cells (Yang and Yazulla, 1988a), though they don't appear to contribute to the receptive field surround (Hare and Owen, 1996). These glycine receptors may be the target of glycinergic interplexiform cells, which have been shown to affect the dendrites of bipolar cells (Maple and Wu, 1998), perhaps to regulate the gain of signal transmission between photoreceptors and bipolar cells (Jiang et al, 2014).…”

What the salamander eye has been telling the vision scientist’s brain

“…There also have been observations of glycine receptors at the dendrites of bipolar cells [ 140 ], though they don’t appear to contribute to the receptive field surround [ 151 ]. These glycine receptors may be the target of glycinergic interplexiform cells, which have been shown to affect the dendrites of bipolar cells [ 152 ], perhaps to regulate the gain of signal transmission between photoreceptors and bipolar cells [ 153 ].…”